Role of Akt signaling in resistance to DNA-targeted therapy

Table 4 Clinical trials on phosphatidylinositol 3 kinase/Akt inhibitors in combination with DNA-targeted agents

PI3K/Akt inhibitor	Target(s)	Combination arm(s)	Condition	Trial phase/status	Trial/registration
MK-2206	Akt	Carboplatin + paclitaxel, docetaxel, erlotinib	Locally advanced, metastatic solid tumors	I/completed (published)	NCT00848718/February 2009[170]
		Paclitaxel, trastuzumab	HER2-overexpressing advanced solid tumors	I/completed (abstract is published)	NCT01235897/November 2010[171]
		Paclitaxel	Adult solid neoplasm,	I/ongoing (unpublished)	NCT01263145/December 2010
			recurrent or metastatic breast cancer
Perifosine	PI3K/Akt	Docetaxel, prednisone	Neoplasms	I/completed (abstract is published)	NCT00399087/November 2006[172]
		Docetaxel	Recurrent ovarian cancer	I/completed (abstract is published)	NCT00431054/February 2007[173]
		Paclitaxel	Neoplasms	I/completed (abstract is published)	NCT00399126/November 2006[174]
		Gemcitabine	Neoplasms	I/completed (abstract is published)	NCT00398697/November 2006[175]
		Radiation	Solid tumors	I/published	Vink et al[176]
		Radiation	Biochemically recurrent, hormone-sensitive prostate cancer with previous prostatectomy and/or radiation therapy	II/published	Chee et al[177]
BEZ235	PI3K/mTOR	BEZ235 + paclitaxel, BKM120 + paclitaxel, BEZ235 + paclitaxel + trastuzumab, BKM120 + paclitaxel + trastuzumab	Metastatic or locally advanced solid tumors	I/completed (abstract is published)	NCT01285466/January 2011[178]
		Paclitaxel	Inoperable locally advanced breast cancer, metastatic breast cancer	I and II/completed (abstract is published)	NCT01495247/September 2011[179]

HER2: Human epidermal growth factor receptor 2; PI3K: Phosphatidylinositol 3 kinase; mTOR: Mammalian target of rapamycin.